A novel synthetic Arg-Gly-Asp-containing peptide cyclo(-RGDf==V-) is the potent inhibitor of angiogenesis

Biochem Biophys Res Commun. 2001 Nov 2;288(3):711-7. doi: 10.1006/bbrc.2001.5809.

Abstract

Arg-Gly-Asp (RGD)-containing peptide is a ligand for integrin alpha(V)beta3 and acts as an angiogenic inhibitor. A novel cyclic RGD peptide, cyclo(-RGDf==V-) (f==V), was synthesized and its biological activities were characterized and compared with its analogs, cyclo(-RGDfV-) (fV) and cyclo(-RGDf-MeV-) (fMeV). It bound to integrin alpha(V)beta3 with almost the same affinity as the fV and fMeV analogs. All three compounds inhibited the adhesion and growth of HUVEC cells in a dose-dependent manner in vitro. Out of three, fMeV had the strongest effect, f==V was almost as strong as fMeV, and fV had the least effect. However, in vivo, f==V significantly decreased the intratumoral microvessel density (MVD) in the DLD-1 (human colon cancer cell) inoculated mice, while fMeV had little effect. These results suggest the potential usefulness of the cyclo(-RGDf==V-) as an antiangiogenic agent for clinical use in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiology
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / drug therapy
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology*
  • Oligopeptides / pharmacology*
  • Oligopeptides / therapeutic use
  • Peptides, Cyclic / pharmacology*
  • Peptides, Cyclic / therapeutic use

Substances

  • Oligopeptides
  • Peptides, Cyclic
  • arginyl-glycyl-aspartic acid